Acadesine Circumvents Azacitidine Resistance in Myelodysplastic Syndrome and Acute Myeloid Leukemia
2020
Cluzeau, Thomas | Furstoss, Nathan | Savy, Coline | El Manaa, Wejdane | Zerhouni, Marwa | Blot, Lauriane | Calleja, Anne | Dufies, Maeva | Dubois, Alix | Ginet, Clemence | Mounier, Nicolas | Garnier, Georges | Raynaud, Sophie | Rohrlich, Pierre Simon | Peterlin, Pierre | Stamatoullas, Aspasia | Chermat, Fatiha | Fenaux, Pierre | Jacquel, Arnaud | Robert, Guillaume | Auberger, Patrick | Hôpital Saint-Louis ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7) | Centre méditerranéen de médecine moléculaire (C3M) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA) | Fondation ARC pour la recherche sur le cancer | Hôpital l'Archet | BIOlogie et GEstion des Risques en agriculture (BIOGER) ; Institut National de la Recherche Agronomique (INRA)-AgroParisTech | Université Paris Saclay (COmUE) | Institut de Recherche sur le Cancer et le Vieillissement (IRCAN) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA) | Hôpital Princesse Grace [Monaco] | Centre hospitalier universitaire de Nantes (CHU Nantes) | Service d'hématologie ; Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon) | Nuclear Oncology (CRCINA-ÉQUIPE 13) ; Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA) ; Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes) | Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel) | Hopital Saint-Louis [AP-HP] (AP-HP) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | Université Paris Diderot - Paris 7 (UPD7) | Université Sorbonne Paris Cité (USPC)
International audience
اظهر المزيد [+] اقل [-]إنجليزي. Myelodysplastic syndrome (MDS) defines a group of heterogeneous hematologic malignancies that often progresses to acute myeloid leukemia (AML). The leading treatment for high-risk MDS patients is azacitidine (Aza, Vidaza®), but a significant proportion of patients are refractory and all patients eventually relapse after an undefined time period. Therefore, new therapies for MDS are urgently needed. We present here evidence that acadesine (Aca, Acadra®), a nucleoside analog exerts potent anti-leukemic effects in both Aza-sensitive (OCI-M2S) and resistant (OCI-M2R) MDS/AML cell lines in vitro. Aca also exerts potent anti-leukemic effect on bone marrow cells from MDS/AML patients ex-vivo. The effect of Aca on MDS/AML cell line proliferation does not rely on apoptosis induction. It is also noteworthy that Aca is efficient to kill MDS cells in a co-culture model with human medullary stromal cell lines, that mimics better the interaction occurring in the bone marrow. These initial findings led us to initiate a phase I/II clinical trial using Acadra® in 12 Aza refractory MDS/AML patients. Despite a very good response in one out 4 patients, we stopped this trial because the highest Aca dose (210 mg/kg) caused serious renal side effects in several patients. In conclusion, the side effects of high Aca doses preclude its use in patients with strong comorbidities.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل Institut national de la recherche agronomique